Biomarker discovery and validation is a critical component for improving diagnosis and management of diseases. In the field of Infectious Diseases, the dramatic impact that biomarkers can have on improving medical care can be illustrated by HIV RNA assays. These assays have enabled identification of individuals at very early stages of infection, those at risk for more rapid progression to AIDS and death, and those who fail antiretroviral therapy (ART). The state of biomarker validation in many other areas has not approached this level of success. For example, recent data have identified that approximately half of people living with HIV (PLWH) have HIV-associated neurocognitive disorders (HAND) despite undetectable HIV RNA levels, clearly indicating the need for new biomarkers to improve understanding of pathogenesis and clinical management. The UCSD HIV Neurobehavioral Research Center (HNRC) has been a leader in NeuroAIDS for more than two decades and has published important biomarker findings, including data linking biomarkers to HAND and changes with ART. The HNRC has a large repository of data and specimens from this long period of focused work and this will serve as the basis for ongoing biomarker work, including existing, NIH-funded projects. The overarching aim of this award will be to use modern measurement methods to identify biomarkers that will favorably impact diagnosis and management of diseases, particularly neurologic complications of HIV. The primary scientific objective of this Shared Instrumentation Grant will be to identify and validate biomarkers that will inform pathogenesis and clinical management of HAND and important neurotoxic comorbid conditions, such as co-infections and substance use. The primary service objective will be to support other projects at UCSD, not only by sharing the instrument with other investigators but by providing expertise in assay performance, specimen management, and data analysis. The selected instrument for purchase is the Millipore FlexMAP 3D assay system. The system includes a multiplex suspension array reader, an automated plate washer, and specialized software to calibrate the instrument and read results. Compared with older suspension array systems, the FlexMAP 3D is capable of measuring substantially more analytes per well, has much improved accuracy, substantially expanded dynamic range, and higher throughput. Together, these attributes will improve the accuracy of our analyses while better conserving our precious specimen resource and enabling more efficient time management. If successful, this award will lead to better understanding of how diseases injure the brain, will identify biomarkers that predict risk for HAND, and improve the management of this condition and others.